Bartonella quintana endocarditis in a child from Northern Manitoba, Canada

We describe a case of Bartonella quintana endocarditis in an 11-year-old child from Northern Manitoba, Canada. This case demonstrates the neglected endemicity of B. quintana in Northern Canada and highlights the need for improved case finding and elucidation of specific risk factors for B. quintana infection in the Canadian North. Considering B. quintana’s predominant transmission via body lice ectoparasitosis, we hypothesize that B. quintana’s endemicity in Northern Canada is linked to inadequate access to suitable housing and running water among remote communities in the Canadian North.

Ten days after admission, the patient developed worsening heart failure and was urgently transferred to the Stollery Children's Hospital in Edmonton, Alberta. He underwent a Ross procedure the following day, and his aortic valve was successfully replaced. His antibiotics were changed to piperacillin-tazobactam and gentamicin. Pathology of the explanted aortic valve demonstrated vegetations over 80% of the tissue. The specimen demonstrated areas of fibromyxoid tissue, calcification, and patchy lymphocytic infiltrate. Gram stain of the tissue showed polymorphonuclear cells and no bacteria. Bartonella quintana was subsequently identified by 16S rRNA sequencing of a portion of the explanted aortic valve followed by DNA sequencing of the resulting amplicon. BLAST analysis of the DNA sequence demonstrated 100% homology to B. quintana (see S1 Appendix). Results for B. quintana serology, using a semiquantitative indirect immunofluorescent antibody assay (Focus Diagnostics), were subsequently reported as positive (IgG titer 1:1024) [1].
Seven days after surgery, the patient was transferred back to Winnipeg's HSC where his antibiotics were changed to gentamicin (1 mg/kg/dose IV q8h) and doxycycline (100 mg PO BID). He received 4 weeks of gentamicin and 6 weeks of doxycycline. At follow-up 3 weeks and 2 months following discharge, the patient had no signs of heart failure or ongoing infection.

Ethics statement
This case report was approved by the University of Manitoba (Bannatyne Campus) Research Ethics Board (HS25337:H2022:030). Formal written consent was obtained from the patient's parent.

Discussion
B. quintana is a fastidious, gram-negative, intraerythrocytic bacillus [2]. Due to its niche within erythrocytes and its slow replication time, Bartonella species evade identification by routine blood culture methods [2,3]. B. quintana is predominantly transmitted by body lice feces, entering the bloodstream through microabrasions of the skin [2]. While originally identified among soldiers in the trenches of World War I, B. quintana has emerged among urban populations experiencing homelessness, leading to the designation of "urban trench fever" [4,5]. B. quintana is a major cause of culture-negative endocarditis and is associated with chronic bacteremia that may last many months [6].
B. quintana has recently been reported in rural Northern Canada. The first published rural Canadian case of B. quintana endocarditis was acquired in Northern Manitoba in 2014 in a remote Cree community, 500 kilometers from the community where this pediatric patient lived [7]. In 2020, 2 additional cases of B. quintana endocarditis were diagnosed in individuals from a different Oji-Cree community, 75 kilometers from the one presented here [8]. In 2021, a fourth case of B. quintana endocarditis was described in a patient from rural Northern Alberta [9]. Our case represents the fifth published case of B. quintana endocarditis in rural Northern Canada, the first pediatric case of B. quintana in Canada and the first pediatric case of B. quintana endocarditis acquired in a high-income country [10].
In 2019, a case of urban B. quintana endocarditis was described in a man experiencing homelessness in a Canadian city [11]. This case, along with a review of 12 other North American cases of B. quintana endocarditis, occurred outside the hypothesized "Europe-African gradient" [11,12]. This concept describes a latitudinal gradient between areas of high B. quintana prevalence in Africa and low prevalence in Northern Europe [11,12]. The increasing number of B. quintana endocarditis cases in Northern Canada defy the "Europe-African gradient" and suggest that this gradient may be an economic one, rather a latitudinal one: Northern populations experiencing poverty may demonstrate similar rates of B. quintana to Southern populations.
Pediculosis was not described in any of the rural Canadian cases of B. quintana endocarditis. While B. quintana has been detected in alternate vectors such as cat fleas, most studies suggest that B. quintana is a specialist adapted to the louse vector and human host. [2,[13][14][15] A nonhuman reservoir and nonlouse vectors remain possible, although undescribed in the Canadian context.
Due to its predominant link with body lice ectoparasitosis, B. quintana transmission occurs where there is inadequate access to suitable housing and running water, whether that be in historic wartime Europe, urban homeless encampments, or disadvantaged communities of Northern Canada [4,5,[7][8][9]. The patient described here was housed and had not spent significant time in an urban center. As many indigenous communities in Canada are plagued by a housing and running water crisis, we suggest that living in a remote community in Northern Canada is a risk factor for B. quintana [16]. This case highlights the need for active B. quintana case finding and elucidation of specific risk factors for B. quintana acquisition in the Canadian North. We hypothesize that B. quintana's endemicity in rural Northern Canada is linked to inadequate access to running water and neglected pediculosis in certain remote communities.
Supporting information S1 Appendix. DNA sequence of 16S rRNA gene and its associated database search results and DNA alignment first hits. (DOCX)

Key Learning Points
• Bartonella quintana, the bacterium causing trench fever, is predominantly transmitted via body lice, although other modes of transmission in rural Northern Canada have not been fully explored.
• B. quintana evades identification in routine blood cultures, and, thus, diagnosis of B. quintana requires serology and/or molecular testing and communication with the microbiology laboratory.
• B. quintana causes culture-negative endocarditis that may be fatal despite mild symptomatology during preceding prolonged bacteremia.
• While B. quintana is infamous for causing disease among soldiers in the First World War, as well as refugees in underserved camps and urban populations experiencing homelessness, this rural pediatric case highlights the neglected endemicity of trench fever in rural Northern communities in Canada.